Method for treating morbid obesity

ABSTRACT

A method for treating morbid obesity in a body of a mammal having a gastrointestinal tract extending through a stomach and a pyloric sphincter and a wall forming the stomach and pyloric sphincter. At least one implant is formed in the wall in the vicinity of the pyloric sphincter to inhibit emptying of the stomach.

This application is a continuation application of U.S. patentapplication Ser. No. 14/087,216, filed Nov. 22, 2013, now U.S. Pat. No.8,968,177, which is a continuation application of U.S. patentapplication Ser. No. 13/243,230, filed Sep. 23, 2011, now U.S. Pat. No.8,591,598, which is a continuation application of U.S. patentapplication Ser. No. 12/715,057, filed Mar. 1, 2010, now U.S. Pat. No.8,048,170, which is a continuation application of U.S. patentapplication Ser. No. 12/102,820, filed Apr. 14, 2008, now U.S. Pat. No.7,691,152, which is a continuation of application Ser. No. 11/435,462filed May 16, 2006, now U.S. Pat. No. 7,364,591, which is a continuationof application Ser. No. 10/964,596 filed Oct. 12, 2004, now U.S. Pat.No. 7,044,979, which is a continuation of application Ser. No.10/386,241, filed Mar. 10, 2003, now U.S. Pat. No. 6,802,868, which is acontinuation of application Ser. No. 09/709,236 filed Nov. 10, 2000, nowU.S. Pat. No. 6,540,789, which claims priority to U.S. provisionalpatent application Ser. No. 60/212,072 filed Jun. 15, 2000, all of whichare incorporated by reference in their entireties herein.

This invention pertains to the treatment of morbid obesity.

Numerous modalities are purported to treat morbid obesity. These includepatient-specific dietary restrictions and nutritional supplementation,abdominoplasty or panniculectomy, gastric banding and/or stapling andthe more invasive and surgically aggressive gastric bypass. There is aneed for a method which is less invasive and more clinically efficaciousin treating morbid obesity.

In general, it is an object of the present invention to provide a methodfor creating implants in natural body cavities accessible by naturalbody openings and more preferably in gastrointestinal tract passagewaysin order to treat morbid obesity.

Another object of the invention is to provide a method of the abovecharacter for enhancing the pylorus.

Another object of the invention is to provide a method of the abovecharacter for limiting distensibility of the stomach and prolongingsatiety.

Another object of the invention is to provide a method of the abovecharacter which is safe and relatively non-invasive.

Additional objects and features of the invention will appear from thefollowing description from which the preferred embodiments are set forthin detail in conjunction with the accompanying drawings.

FIG. 1 is a schematic view with a device in place in the esophagus andstomach for performing the method of the present invention.

FIG. 2 is a frontal view, partially cut away, of the lower esophagus,stomach and pylorus with implants formed therein in accordance with themethod of the present invention.

FIG. 3 is a cross-sectional view of the stomach taken along the line 3-3of FIG. 2.

FIG. 4 is a frontal view, similar to FIG. 2 and partially cut away, ofthe lower esophagus, stomach and pylorus with implants formed therein inaccordance with the method of the present invention.

FIG. 5 is a frontal view of the lower esophagus, stomach and pyloricregion treated by an alternative method of the present invention.

FIG. 6 is a cross-sectional view of the pyloric region and stomach takenalong the line 6-6 of FIG. 5.

FIG. 7 is a frontal view of the lower esophagus, stomach and pyloricregion treated by an alternative method of the present invention.

In general, a method for treating morbid obesity in a body of a mammalhaving a gastrointestinal tract extending through a stomach and apyloric sphincter formed by a wall is provided. At least one implant isformed in the wall in the vicinity of the pyloric sphincter to inhibitemptying of the stomach.

The method of the present invention is for use in a natural body cavitysuch as the gastrointestinal tract in a body of a mammal. A portion of ahuman body 21 is shown in FIG. 1 and has an internal cavity in the formof the passage of the esophagus 22 extending through a lower esophagealsphincter 23 to a stomach 24 and a pyloric sphincter 25. Such cavity isaccessible by a natural body opening in the form of mouth 26 and isdefined by wall 27. Esophagus 22, stomach 24 and pyloric sphincter 25form part of the gastrointestinal tract of body 21 that extends frommouth 26 to an anus (not shown). The pylorus 25 is a one-way sphincterthat serves as the anatomical junction between stomach 24 and theduodenum.

Esophageal mucosa 28 serves as the inner layer of the intraluminal wall27 in esophagus 22 and the gastric mucosa 29 serves as the inner layerof the intramural wall 27 in stomach 24 and pylorus 25. Esophagealmucosa 28 and gastric mucosa 29 meet at the squamous columnar junction(not shown). Wall 27 has a muscle layer comprising a layer of circularmuscle 32 extending beneath mucosa layers 28 and 29 and a layer oflongitudinal muscle 33 beneath circular muscle 32. Muscle layers 32 and33 extend around esophagus 22, stomach 24 and pylorus 25. Wall 27further includes a submucosal layer or submucosa 34 extending betweenmucosa 29 and muscle layers 32 and 33. A submucosal space, that is apotential space, can be created between submucosa 34 and circular musclelayer 32 by the separation of layer 28 or 29 from muscle layer 32. Inaddition, as with any muscle, wall 27 includes an intramuscularpotential space, that is a space which can be created intramuscularly bydistension and separation of muscle fibers within a single muscle. Wall27 has a depth or thickness which includes at least mucosal layers 28and 29, submucosal layer 34, circular muscle layer 32 and longitudinalmuscle layer 33.

The method of the present invention can be performed with any of theapparatus disclosed U.S. Pat. No. 6,251,063 and U.S. Pat. No. 6,238,335,the entire contents of each of which are incorporated herein by thisreference. In general, a suitable apparatus or medical device 41includes a probe member or probe 42 having an optical viewing device(not shown). Only a portion of device 41 has been shown in FIG. 1. Aconventional or other suitable gastroscope or endoscope can be used asor with probe 42. A needle assembly 43 is slidably carried by probe 42.Needle assembly 43 can be of any conventional type, such as a modifiedsclerotherapy needle similar to the Bard® Flexitip™ needle manufacturedby C.R. Bard, Inc. of Billerica, Md., and includes a needle member orneedle 44 and a protective sleeve (not shown). Device 41 furtherincludes a supply assembly (not shown) mounted to the proximal endportion of needle assembly 43. The supply assembly is secured to theproximal extremity of needle assembly 43 and can include a conventionalsyringe for introducing a liquid or solution through needle 44. Thesupply assembly optionally includes second and third reservoirs in theform of second and third syringes. The second syringe is filled withdimethyl sulfoxide (DMSO) or any other suitable liquid. The thirdsyringe is filled with a saline solution or any other suitable aqueousor physiological solution.

In the method of the present invention, at least one implant formingmaterial is introduced into the wall 27 of the gastrointestinal tract toform at least one implant therein. Exemplary implant-forming materialsinclude any suitable material from which an implant can be formed when afluid, separately or in conjunction with another fluid, is introducedinto the tissue of a body. Other suitable implantable materials includeany material capable of being delivered through a needle, solutions,suspensions, slurries, biodegradable or nonbiodegradable materials andtwo part or other mixtures. Exemplary implantable materials includeinjectable bioglass as described in Walker et al., “Injectable Bioglassas a Potential Substitute for Injectable PolytetrafluorethyleneParticles”, J. Urol., 148:645-7, 1992, small particle species such aspolytetrafluoroethylene (PTFE) particles in glycerine such as Polytef®,biocompatible compositions comprising discrete, polymeric and siliconerubber bodies such as described in U.S. Pat. Nos. 5,007,940, 5,158,573and 5,116,387 to Berg, biocompatible compositions comprising carboncoated beads such as disclosed in U.S. Pat. No. 5,451,406 to Lawin,collagen and other biodegradable material of the type disclosed in U.S.Pat. No. 4,803,075 to Wallace et al. and other known injectablematerials.

Although aqueous or nonaqueous solutions are amongst the fluids that canbe used, an inert, nonresorbable material is preferred. Preferrednonaqueous solutions are any of the solutions disclosed in InternationalApplication No. PCT/US99/29427 filed Dec. 10, 1999, the entire contentof which is incorporated herein by this reference. One such materialcomprises at least one solution which when introduced into the bodyforms a nonbiodegradable solid. As used herein, a solid means anysubstance that does not flow perceptibly under moderate stress, has adefinite capacity for resisting forces which tend to deform it (such ascompression, tension and strain) and under ordinary conditions retains adefinite size and shape; such a solid includes, without limitation,spongy and/or porous substances. One such embodiment of the at least onesolution is first and second solutions which when combined in the bodyform the nonbiodegradable solid. Another such embodiment is a nonaqueoussolution which can be introduced into the body as a liquid and fromwhich a solid thereafter precipitates. A preferred embodiment of such anonaqueous solution is a solution of a biocompatible polymer and abiocompatible solvent which can optionally include a contrast agent forfacilitating visualization of the solution in the body.

A particularly preferred implant forming solution is a compositioncomprising from about 2.5 to about 8.0 weight percent of a biocompatiblepolymer, from about 52 to about 87.5 weight percent of a biocompatiblesolvent and optionally from about 10 to about 40 weight percent of abiocompatible contrast agent having a preferred average particle size ofabout 10 μm or less. It should be appreciated that any percents statedherein which include a contrast agent would be proportionally adjustedwhen the contrast agent is not utilized. Any contrast agent ispreferably a water insoluble biocompatible contrast agent. The weightpercent of the polymer, contrast agent and biocompatible solvent isbased on the total weight of the complete composition. In a preferredembodiment, the water insoluble, biocompatible contrast agent isselected from the group consisting of barium sulfate, tantalum powderand tantalum oxide. In still a further preferred embodiment, thebiocompatible solvent is dimethylsulfoxide (DMSO), ethanol, ethyllactate or acetone.

The term “biocompatible polymer” refers to polymers which, in theamounts employed, are non-toxic, chemically inert, and substantiallynon-immunogenic when used internally in the patient and which aresubstantially insoluble in physiologic liquids. Suitable biocompatiblepolymers include, by way of example, cellulose acetates (includingcellulose diacetate), ethylene vinyl alcohol copolymers, hydrogels(e.g., acrylics), poly(C₁-C₆) acrylates, acrylate copolymers, polyalkylalkacrylates wherein the alkyl and alk groups independently contain oneto six carbon atoms, polyacrylonitrile, polyvinylacetate, celluloseacetate butyrate, nitrocellulose, copolymers of urethane/carbonate,copolymers of styrene/maleic acid, and mixtures thereof. Copolymers ofurethane/carbonate include polycarbonates that are diol terminated whichare then reacted with a diisocyanate such as methylene bisphenyldiisocyanate to provide for the urethane/carbonate copolymers. Likewise,copolymers of styrene/maleic acid refer to copolymers having a ratio ofstyrene to maleic acid of from about 7:3 to about 3:7. Preferably, thebiocompatible polymer is also non-inflammatory when employed in situ.The particular biocompatible polymer employed is not critical and isselected relative to the viscosity of the resulting polymer solution,the solubility of the biocompatible polymer in the biocompatiblesolvent, and the like. Such factors are well within the skill of theart.

The polymers of polyacrylonitrile, polyvinylacetate, poly(C₁-C₆)acrylates, acrylate copolymers, polyalkyl alkacrylates wherein the alkyland alk groups independently contain one to six carbon atoms, celluloseacetate butyrate, nitrocellulose, copolymers of urethane/carbonate,copolymers of styrene/maleic acid and mixtures thereof typically willhave a molecular weight of at least about 50,000 and more preferablyfrom about 75,000 to about 300,000.

Preferred biocompatible polymers include cellulose diacetate andethylene vinyl alcohol copolymer. In one embodiment, the cellulosediacetate has an acetyl content of from about 31 to about 40 weightpercent. Cellulose diacetate polymers are either commercially availableor can be prepared by art recognized procedures. In a preferredembodiment, the number average molecular weight, as determined by gelpermeation chromatography, of the cellulose diacetate composition isfrom about 25,000 to about 100,000 more preferably from about 50,000 toabout 75,000 and still more preferably from about 58,000 to 64,000. Theweight average molecular weight of the cellulose diacetate composition,as determined by gel permeation chromatography, is preferably from about50,000 to 200,000 and more preferably from about 100,000 to about180,000. As is apparent to one skilled in the art, with all otherfactors being equal, cellulose diacetate polymers having a lowermolecular weight will impart a lower viscosity to the composition ascompared to higher molecular weight polymers. Accordingly, adjustment ofthe viscosity of the composition can be readily achieved by mereadjustment of the molecular weight of the polymer composition.

Ethylene vinyl alcohol copolymers comprise residues of both ethylene andvinyl alcohol monomers. Small amounts (e.g., less than 5 mole percent)of additional monomers can be included in the polymer structure orgrafted thereon provided such additional monomers do not alter theimplanting properties of the composition. Such additional monomersinclude, by way of example only, maleic anhydride, styrene, propylene,acrylic acid, vinyl acetate and the like.

Ethylene vinyl alcohol copolymers are either commercially available orcan be prepared by art recognized procedures. Preferably, the ethylenevinyl alcohol copolymer composition is selected such that a solution of8 weight-volume percent of the ethylene vinyl alcohol copolymer in DMSOhas a viscosity equal to or less than 60 centipoise at 20° C. and morepreferably 40 centipoise or less at 20° C. As is apparent to one skilledin the art, with all other factors being equal, copolymers having alower molecular weight will impart a lower viscosity to the compositionas compared to higher molecular weight copolymers. Accordingly,adjustment of the viscosity of the composition as necessary for catheterdelivery can be readily achieved by mere adjustment of the molecularweight of the copolymer composition.

As is also apparent, the ratio of ethylene to vinyl alcohol in thecopolymer affects the overall hydrophobicity/hydrophilicity of thecomposition which, in turn, affects the relative watersolubility/insolubility of the composition as well as the rate ofprecipitation of the copolymer in an aqueous solution. In a particularlypreferred embodiment, the copolymers employed herein comprise a molepercent of ethylene of from about 25 to about 60 and a mole percent ofvinyl alcohol of from about 40 to about 75, more preferably a molepercent of ethylene of from about 40 to about 60 and a mole percent ofvinyl alcohol of from about 40 to about 60.

The term “contrast agent” refers to a biocompatible (non-toxic)radiopaque material capable of being monitored during injection into amammalian subject by, for example, radiography. The contrast agent canbe either water soluble or water insoluble. Examples of water solublecontrast agents include metrizamide, iopamidol, iothalamate sodium,iodomide sodium, and meglumine. The term “water insoluble contrastagent” refers to contrast agents which are insoluble in water (i.e., hasa water solubility of less than 0.01 milligrams per milliliter at 20°C.) and include tantalum, tantalum oxide and barium sulfate, each ofwhich is commercially available in the proper form for in vivo use andpreferably having a particle size of 10 μm or less. Other waterinsoluble contrast agents include gold, tungsten and platinum powders.Methods for preparing such water insoluble biocompatible contrast agentshaving an average particle size of about 10 μm or less are describedbelow. Preferably, the contrast agent is water insoluble (i.e., has awater solubility of less than 0.01 mg/ml at 20° C.).

The term “encapsulation” as used relative to the contrast agent beingencapsulated in the precipitate is not meant to infer any physicalentrapment of the contrast agent within the precipitate much as acapsule encapsulates a medicament. Rather, this term is used to meanthat an integral coherent precipitate forms which does not separate intoindividual components, for example into a copolymer component and acontrast agent component.

The term “biocompatible solvent” refers to an organic material liquid atleast at body temperature of the mammal in which the biocompatiblepolymer is soluble and, in the amounts used, is substantially non-toxic.Suitable biocompatible solvents include, by way of example,dimethylsulfoxide, analogues/homologues of dimethylsulfoxide, ethanol,ethyl lactate, acetone, and the like. Aqueous mixtures with thebiocompatible solvent can also be employed provided that the amount ofwater employed is sufficiently small that the dissolved polymerprecipitates upon injection into a human body. Preferably, thebiocompatible solvent is ethyl lactate or dimethylsulfoxide.

The compositions employed in the methods of this invention are preparedby conventional methods whereby each of the components is added and theresulting composition mixed together until the overall composition issubstantially homogeneous. For example, sufficient amounts of theselected polymer are added to the biocompatible solvent to achieve theeffective concentration for the complete composition. Preferably, thecomposition will comprise from about 2.5 to about 8.0 weight percent ofthe polymer based on the total weight of the composition and morepreferably from about 4 to about 5.2 weight percent. If necessary,gentle heating and stirring can be used to effect dissolution of thepolymer into the biocompatible solvent, e.g., 12 hours at 50° C.

Sufficient amounts of the contrast agent are then optionally added tothe biocompatible solvent to achieve the effective concentration for thecomplete composition. Preferably, the composition will comprise fromabout 10 to about 40 weight percent of the contrast agent and morepreferably from about 20 to about 40 weight percent and even morepreferably about 30 to about 35 weight percent. When the contrast agentis not soluble in the biocompatible solvent, stirring is employed toeffect homogeneity of the resulting suspension. In order to enhanceformation of the suspension, the particle size of the contrast agent ispreferably maintained at about 10 μm or less and more preferably at fromabout 1 to about 5 μm (e.g., an average size of about 2 μm). In onepreferred embodiment, the appropriate particle size of the contrastagent is prepared, for example, by fractionation. In such an embodiment,a water insoluble contrast agent such as tantalum having an averageparticle size of less than about 20 microns is added to an organicliquid such as ethanol (absolute) preferably in a clean environment.Agitation of the resulting suspension followed by settling forapproximately 40 seconds permits the larger particles to settle faster.Removal of the upper portion of the organic liquid followed byseparation of the liquid from the particles results in a reduction ofthe particle size which is confirmed under an optical microscope. Theprocess is optionally repeated until a desired average particle size isreached.

The particular order of addition of components to the biocompatiblesolvent is not critical and stirring of the resulting suspension isconducted as necessary to achieve homogeneity of the composition.Preferably, mixing/stirring of the composition is conducted under ananhydrous atmosphere at ambient pressure. The resulting composition isheat sterilized and then stored preferably in sealed amber bottles orvials until needed.

Each of the polymers recited herein is commercially available but canalso be prepared by methods well known in the art. For example, polymersare typically prepared by conventional techniques such as radical,thermal, UV, gamma irradiation, or electron beam induced polymerizationemploying, as necessary, a polymerization catalyst or polymerizationinitiator to provide for the polymer composition. The specific manner ofpolymerization is not critical and the polymerization techniquesemployed do not form a part of this invention. In order to maintainsolubility in the biocompatible solvent, the polymers described hereinare preferably not cross-linked.

In another particularly preferred embodiment of the nonaqueous solution,the biocompatible polymer composition can be replaced with abiocompatible prepolymer composition containing a biocompatibleprepolymer. In this embodiment, the composition comprises abiocompatible prepolymer, an optional biocompatible water insolublecontrast agent preferably having an average particle size of about 10 μmor less and, optionally, a biocompatible solvent.

The term “biocompatible prepolymer” refers to materials which polymerizein situ to form a polymer and which, in the amounts employed, arenon-toxic, chemically inert, and substantially non-immunogenic when usedinternally in the patient and which are substantially insoluble inphysiologic liquids. Such a composition is introduced into the body as amixture of reactive chemicals and thereafter forms a biocompatiblepolymer within the body. Suitable biocompatible prepolymers include, byway of example, cyanoacrylates, hydroxyethyl methacrylate, siliconprepolymers, and the like. The prepolymer can either be a monomer or areactive oligomer. Preferably, the biocompatible prepolymer is alsonon-inflammatory when employed in situ.

Prepolymer compositions can be prepared by adding sufficient amounts ofthe optional contrast agent to the solution (e.g., liquid prepolymer) toachieve the effective concentration for the complete polymercomposition. Preferably, the prepolymer composition will comprise fromabout 10 to about 40 weight percent of the contrast agent and morepreferably from about 20 to about 40 weight percent and even morepreferably about 30 weight percent. When the contrast agent is notsoluble in the biocompatible prepolymer composition, stirring isemployed to effect homogeneity of the resulting suspension. In order toenhance formation of the suspension, the particle size of the contrastagent is preferably maintained at about 10 μm or less and morepreferably at from about 1 to about 5 μm (e.g., an average size of about2 μm).

When the prepolymer is liquid (as in the case of polyurethanes), the useof a biocompatible solvent is not absolutely necessary but may bepreferred to provide for an appropriate viscosity in the nonaqueoussolution. Preferably, when employed, the biocompatible solvent willcomprise from about 10 to about 50 weight percent of the biocompatibleprepolymer composition based on the total weight of the prepolymercomposition. When a biocompatible solvent is employed, the prepolymericcomposition typically comprises from about 90 to about 50 weight percentof the prepolymer based on the total weight of the composition.

In a particularly preferred embodiment, the prepolymer is cyanoacrylatewhich is preferably employed in the absence of a biocompatible solvent.When so employed, the cyanoacrylate adhesive is selected to have aviscosity of from about 5 to about 20 centipoise at 20° C.

The particular order of addition of components is not critical andstirring of the resulting suspension is conducted as necessary toachieve homogeneity of the composition. Preferably, mixing/stirring ofthe composition is conducted under an anhydrous atmosphere at ambientpressure. The resulting composition is sterilized and then storedpreferably in sealed amber bottles or vials until needed.

Specific embodiments of nonaqueous solutions suitable for use in theapparatus and methods of the invention are described in U.S. Pat. No.5,667,767 dated Sep. 16, 1997, U.S. Pat. No. 5,580,568 dated Dec. 3,1996 and U.S. Pat. No. 5,695,480 dated Dec. 9, 1997 and InternationalPublication Number WO 97/45131 having an International Publication Dateof Dec. 4, 1997, the entire contents of which are incorporated herein bythis reference.

The first aspect of the method of the invention to treat morbid obesityby forming implants in the human gastrointestinal tract may be describedas follows. Let it be assumed that in preparing for the procedure, thegastrointestinal tract of a patient has previously been evaluated byusing any or all techniques and procedures available in the artincluding, but not limited to, upper gastrointestinal radiographicstudies, endoscopy with biopsies and gastrointestinal motility studies.Assuming that the patient's pretreatment evaluation diagnosesintractable morbid obesity which warrants the procedure hereinafterdescribed, the patient can be brought into an outpatient clinic or anoperating room in a hospital. The patient is preferably placed in asemi-recumbent or lateral decubitus position on an operating orexamining table or on a gurney.

After intravenous access has been accomplished and the patient has beenappropriately sedated or anesthetized, the distal extremity of probe 42is introduced through mouth 26 of the patient into stomach 24. In thisregard, the handle of probe 42 is grasped by the physician to introducethe distal extremity of probe 42 into mouth 26 and advance it downesophagus 22 to the vicinity of stomach 24 and pylorus 25, the area tobe treated. The optical viewing device facilities advancement by thephysician of probe 42.

The distal end portion of needle assembly 43 is introduced through probe42 and advanced until the distal end portions of needle 44 and sleeve 46are in the vicinity of the distal extremity of probe 42. Under theguidance of the optical viewing device, the distal extremity of theprobe 42 is maneuvered to a position above or intraluminal of theportion of wall 27 which is to be treated. In a preferred method, thedistal extremity of probe 42 is positioned in the vicinity of pyloricsphincter 25. The physician retracts sleeve 46 relative to needle 44 sothat the distal end portion of needle 44 extends beyond the distal endportion of sleeve 46 a desired amount. The physician primes needle 44with the saline or other aqueous or physiologic solution.

After the physician penetrates wall 27 with the sharpened end of needle44, in one of the methods of the invention a saline or other suitableaqueous or physiological solution, referred to herein as the salinesolution, can be injected into wall 27 and more specifically into one orboth of circular muscle layer 32 and longitudinal muscle layer 33 orbetween the two muscle layers. The saline injection creates anenlargement in the wall 27 that has an internal space filled with thesaline solution. The amount of injected saline solution can range from0.25 to 10 cc and preferably ranges from 1 to 3 cc.

After creation of the saline-filled enlargement, the physician retractsneedle 44 from wall 27, withdraws the remaining saline solution from theneedle passage and cleanses the needle passage with DMSO to ensure thatthe saline solution has been removed from the passage. Removal of thesaline solution from the needle passage and the cleansing of the passagewith DMSO inhibits premature precipitation within syringe of thebiocompatible polymer in the implant forming solution from the DMSO inthe implant forming solution. The needle passage is next primed with theimplanting forming solution.

The physician causes the distal end portion of needle 44 to penetratethe enlargements and extend into the saline filled space therein.Thereafter, the physician causes a preselected amount of the implantforming solution to be introduced through needle 44. The optionalcontrast agent within the implanting forming solution permits theviewing of the solution by means of fluoroscopy. In addition, theintroduction of the implant forming solution into wall 27 can bemonitored by transabdominal or transesophageal ultrasound. The rate ofinjection of the implant forming solution into the space can range from0.1 cc per minute to 10 cc per minute.

Once the implant forming solution has been introduced into wall 27, thebiocompatible polymer of the implant forming solution precipitates toform one or more discrete deposits or solid implants 52 (see FIGS. 2 and4). The amount of implant forming solution injected into wall 27 foreach implant 52 can range from 0.05 cc to 10 cc. The ratio of implantforming solution to saline in the space can range from 2:1 to 1:8 andpreferably ranges from approximately one part implant forming solutionto two to three parts saline solution. In one embodiment, the spacecreated by the saline solution predefines the configuration of theprecipitant or implant 52. The discrete implant 52 can occupy less thanall of the space or, alternatively, more implant forming solution thansaline can be introduced into wall 27 so that the discrete implant 52more than fills the space created by the saline. After completion of theinjection of implant forming solution and the solidification of thebiocompatible polymer, the remaining solution within the space disperseswithin body 21 and the space contracts about implant 52.

It has been found that an injection of a suitable aqueous or physiologicsolution such as a saline solution into wall 27 prior to the injectionof the augmenting solution creates a space (not shown) which is morebulbous than elongate in configuration. The injection of the implantforming solution into such saline filled space facilitates rapidprecipitation and enhanced solidification of the biocompatible polymer.This rapid solidification facilitates the desired shaping of implant 52,which is shown in FIG. 2 as being somewhat spherical and elongated inshape. It has also been found that the saline solution facilitates thecreation of a relatively soft and spongy implant 52.

The injection of the saline solution into the wall 27 prior to theinjection of the implant forming solution serves to condition or preparethe tissue in the wall 27, that is to help the wall 27 receive theimplant forming solution and thus facilitate implantation of thebiocompatible polymer. In this regard, the saline solution enhances thebody's acceptance of the implant forming solution by minimizing therejection response to the implant 52 and contributing to the body'shealing response to the implant. The saline solution also enhances theresolution of any irritative or inflammatory reaction of the body to theDMSO. It should be appreciated that the invention is broad enough tocover any introduction of a solution into the tissue of the body tocondition or prepare the tissue for treatment and thereafter performinga treatment on the tissue. Although the conditioning solution has beendescribed as a saline solution, antibiotics and/or anti-inflammatoriescan be introduced locally to condition the tissue.

The use of a saline solution as discussed above also facilitates therapid dispersion of the DMSO from the implant forming solution thusdiluting any local irritant effect of the DMSO. The saline solutionfurther acts as a heat sink for the heat of dissolution of the solvent.

A plurality of implants 52 are preferentially created in wall 27 in themethod of the invention. The number and configuration of implants 52formed in wall 27 can vary. Specific examples of implant configurationsare disclosed in U.S. Pat. No. 6,251,063. In one preferred method of theinvention, a plurality of implants 52 are created in wall 27 in thevicinity of pyloric sphincter 25 to create a stenosis in pyloricsphincter 25 and/or a reduction in distensibility in thegastrointestinal wall forming pyloric sphincter 25 by bulking,thickening or tightening the same. The implants 52 are each somewhatpillow-like in shape and are preferably circumferentially spaced-apartor disposed around the periphery of pylorus 25. More specifically,implants 52 are disposed substantially in a plane extendingperpendicularly to a longitudinal axis extending along the centerline ofpylorus 25. An exemplary rosette of four implants 52 spaced-apart aroundthe center of the rosette at approximately 90° intervals is partiallyshown in FIGS. 2 and 4. It should be appreciated, however, that lessthan four or greater than four implants 52 can be provided and formed inwall 27 and can be circumferentially spaced-apart at approximately equalangular intervals or asymmetrically disposed about the center line ofpylorus 25. A plane of implants can be disposed above, below and/or atpylorus 25. As indicated, in other configurations, implants can beformed which are not disposed in a single plane. A plurality of implantsmay also be formed in additional planes spaced apart from a first planeof implants. Such an array of implants can be longitudinally centered onpylorus 25. In another configuration, a single implant can be providedfor augmenting or partially or completely coapting pylorus 25. Implants52 which merge with adjacent implants 52 in wall 27 are within the scopeof the present invention.

The implantable material can be injected into any layer of the wall,such as mucosa 29 or submucosa 34, although it is preferred that theimplantable material be deposited into one or both of circular andlongitudinal muscles 32 and 33 in the wall. The shape of the implantscan vary. In this regard, the implants can be discrete depositions thatare circular or ball-like or that have any other shape. Alternatively,the implants can be depositions with finger-like or lake-like extensionsor, as disclosed in U.S. Pat. No. 6,251,064, the entire content of whichis incorporated herein by this reference, extend arcuately around atleast a portion of pylorus 25 and possibly completely around pylorus 25in a ring-shaped or ring-like manner.

The procedure of the first aspect of the invention serves to increasegastric emptying times and thus prolong periods of satiety. Althoughimplants 52 do not make a non-functioning pyloric sphincter, they docreate some level of stenosis to delay gastric emptying and thus causelonger periods of gastric distention. Gastric fullness causes longerperiods of satiety and reduction of the appetite.

The optional contrast agent in the implants permits the implants to bemonitored after completion of the procedure described above. Thus thestability of the implant and its configuration can be observed overtime. Further procedures can be performed to supplement previouslyformed implants. It should be appreciated that the implants of thepresent invention can be used as delivery vehicles for other materialssuch as radio-isotopes, chemotherapeutic agents, anti-inflammatoryagents and/or antibiotics.

Although the method of the invention has been described as including theformation of a space by a saline solution injected into the wall 27prior to an injection of implant forming solution into the wall 27, itshould be appreciated that such space can be formed by other aqueous orphysiologic solutions or by a local anesthetic. Alternatively, theimplant forming solution can be injected into wall 27 without the priorformation of such a space by an injection of saline solution orotherwise. The implant forming solution can also be injected directlyinto the wall 27 without an injection of saline or any other solutionfor any secondary purpose described herein or otherwise. A saline orother aqueous or physiologic solution can optionally be introduced intosuch a space formed by the implant forming solution, that is after theintroduction of the implant forming solution into the wall 27, tofacilitate dispersion of the DMSO or other biocompatible solvent presentin the implant forming solution. It can thus be seen that the inventionis broad enough to cover the introduction of any conditioning solutioninto the tissue after the treatment to facilitate the treatment.

In a second aspect of the method of the present invention, which can beperformed separately or in combination with the first aspect of theinvention, one or more implants are made in the wall of the stomach todecrease the distensibility and contractility of the muscle of thestomach. The implants can be formed by any of the methods discussedabove and can be any of the shapes discussed above. If more than oneimplant is made, any of the configurations of implants disclosed abovecan be utilized.

In one preferred method of treatment, one or more implants 52 are madein wall 27 of stomach 24 that extend across one or more portions ofstomach 24. For example, spaced-apart injections can be made in theportions of stomach 24 as shown in FIG. 2. Alternatively, or in additionto such spaced-apart implants 52, an elongate or band-like implant canbe formed, for example in accordance with the method disclosed in U.S.Pat. No. 6,251,064. An exemplary implant configuration 53 shown in FIGS.2 and 4 extends from the top to the bottom of the stomach, that is in avertical, circular or semi-circular fashion, from the upper part orfundus 54 of stomach 24 down towards the lower part or antrum 55 ofstomach 24. An alternate exemplary implant configuration 56, also shownin FIGS. 2 and 4, extends diagonally from a two o'clock position to aneight o'clock position across a portion of stomach 24.

The injections can thus be in a sequential fashion and can each rangefrom 0.25 to 20.0 cubic centimeters and preferably range from 0.5 to 3.0cubic centimeters of implantable material per injection. The injectionscan either be in one portion of the stomach, such as one half or oneside of the stomach, or in a complete semi-circular or spherical fashionaround the front portion, the underneath portion, the back portionand/or the top portion of the stomach. Of course, the one or moreimplants can extend along any irregularly-shaped path along any portionof the wall of the stomach. In addition to or as an alternative to theforegoing, one can make random implantations in a sufficient number ofplaces in the stomach to reduce or stop free propulsive or effectivemovement of the stomach from the back of the stomach towards thepylorus.

The decrease in the distensibility and contractility of the muscle ofstomach 24 resulting from implants 52 formed from the second aspect ofthe invention provoke longer gastric emptying times and thereby prolongperiods of sensation of fullness and satiety, yet at the same time allowfood to pass in a very slow fashion. Such one or more implants 52thereby act in a substantially mechanical manner to alter stomachperistalsis and motility so as to prolong the transit time of materialsin and/or through stomach 24. In so doing, however, reflux pressure onlower esophageal sphincter 23, which is already strained in obesepatients, can be increased.

The first and second aspects of the invention can also use othertechniques for prolonging satiety. One group of such techniques involvespartitioning stomach 24 to reduce its volume. Sutures, staples and gluescan be so used to wall off portions of stomach 24. For example, sutures,staples and/or glues can be placed across any portion of stomach 24,such as along the configurations hereinbefore described, so as to reducethe volume of the stomach. Other such techniques can utilize rings,bands or other mechanical devices placed around lower esophagealsphincter 23 for creating a mechanical valve to reduce reflux throughsphincter 23. Rings, bands and other mechanical devices can also beplaced around the cardia to create a mechanical valve that limitsexpansion of the stomach and thus prolongs satiety.

In a third aspect of the invention, an artificial sphincter can beformed in the wall 27 of the stomach for assisting the lower esophagealsphincter. In one preferred method of the invention, first and secondspaced-apart walls 57 and 58 are formed in stomach 24 to create atubular extension extending through a portion of the stomach 24 (seeFIG. 5). First and second walls 57 and 58 can be formed from anytechnique, such as those discussed above for partitioning stomach 24.Such techniques include sutures, staples and glues. In a preferredembodiment of the third aspect of the invention, first and secondartificial walls 57 and 58 each commence in the vicinity of the entranceof the stomach 24, on opposite sides of the terminus of the esophagus22, and terminate at an artificial sphincter 59 created in wall 27 ofstomach 24 by any of the techniques and by using any of the implantablematerials, in each case, as hereinbefore described. In one exemplaryprocedure, walls 57 and 58 are created by securing together oppositesides of the stomach wall 27 with titanium gastrointestinal staples 61,or any appropriate alloy staples known in the art, as shown in FIG. 5.In this manner, ingested matter is prevented from being propelleddistally, towards the pylorus, without first having to traverseartificial sphincter 59. One or more implants 60 creating new sphincter59, which serves as a secondary antireflux barrier, are preferablyformed in muscle layer 32 of wall 27 so as to reduce the distensibilityof wall 27 and thus form and provide a sphincter mechanism which, inturn, inhibits reflux. The implants 60 are preferably similar toimplants 52 and formed by any of the methods discussed above. Anysuitable configuration of implants 60, such as a plurality ofcircumferentially spaced-apart implants or one or more ring orarcuate-shaped implants, formed in one and preferably in both of theopposite stomach walls 27 can be used for forming the secondarysphincter. Implants 60 are shown in FIGS. 5 and 6 as beingarcuate-shaped implants. Together, walls 57 and 58 and secondarysphincter 59 create an additional barrier which aids LES 23 ininhibiting reflux.

In an alternative embodiment of the third aspect of the presentinvention a portion of stomach 24 is excluded or isolated by one ofwalls 57 and 58. In one exemplary embodiment, first wall 57 preferablyis formed to extend beyond secondary sphincter 59 to the greatercurvature of stomach 24 in order to fully partition stomach 24 andthereby exclude a portion thereof from use and thus prolong satiety.Such extended portion of first wall 57 is shown in phantom lines in FIG.5 and labeled as extended wall 57′ therein.

Each of the aspects of the invention discussed above can be supplementedby the formation of one or more implants in the wall 27 of thegastrointestinal tract in the vicinity of the lower esophageal sphincter23 to enhance the reflux barrier created by the lower esophagealsphincter. Such implants can be formed in the manner discussed abovefrom any suitable implant forming solution. Exemplary procedures andapparatus for forming implants in the vicinity of lower esophagealsphincter 23 are disclosed in U.S. Pat. Nos. 6,251,063 and 6,251,064.

In a fourth aspect of the invention, stomach 24 is provided with asingle wall 71, which is similar to first wall 57 but extends from theupper portion of the stomach 24 adjacent the terminus of the esophagus22 to the greater curvature of stomach 24 so as to fully partitionstomach 24 (see FIG. 7). Wall 71 can be formed from any of thetechniques discussed above, such as sutures, staples or glues, and asshown is formed by staples 61 which secure together opposite sides ofthe stomach wall 27 along the length of the artificial wall 71. At leastone and as shown a plurality of implants 72 are formed in esophagealwall 27 in the vicinity of lower esophageal sphincter 23 for inhibitingreflux from stomach 24 into the esophagus 22. The implants 72 can beformed in any of the manners discussed above from any suitable implantforming material, such as any of the implant forming materials discussedabove and preferably any of the implant forming solutions discussedabove, and can have any of the shapes discussed above. Although theimplants 71 can be formed in any layer of wall 27, the implants arepreferably formed in one or both of circular muscle layer 32 andlongitudinal muscle layer 33 or between the two muscle layers. Where aplurality of implants 71 are formed in wall 28, any suitableconfiguration of implants can be used.

In conjunction with the fourth aspect of the invention, implants canoptionally be formed in wall 27 in the vicinity of the pylorus 25, asdiscussed above in the first aspect of the invention, and/or in wall 27in stomach 24, as discussed above in the second aspect of the invention.As more fully set forth above, the formation of implants 52 in thevicinity of pylorus 25 and/or in wall 27 of stomach 24 prolong periodsof satiety by reducing gastric emptying times.

As discussed above, the implants formed by the various aspects of theinvention serve to alter the wall in which they are formed in amechanical manner, that is by their presence in the wall. The implantsalso act in a nonmechanical manner to alter the characteristics of thewall by modifying sensory motor nervous feedback and control in thewall. It should be appreciated that such a modification of sensory motornervous feedback and control can be accomplished by the implants aloneor in conjunction with an application of energy to such portion of thebody wall. Suitable sources for such energy include radio frequency,laser and microwave energy applied to the wall in a conventional manner,such as by means of a probe or stylet disposed adjacent to the wall orintroduced into the wall.

It should be appreciated that the approach and the access to pylorus 25and stomach 24 for the methods of the present invention can beendoscopic, laparoscopic or by open surgery. The introduction of theimplantable material can be transmucosal, from the inside towards theout, or transserosal, from the outside in. In any event, the injectionsare preferably directed into the muscle of the stomach

The numerical sizes and ranges in the foregoing drawings are merelyexemplary and not intended to be limiting of the purview of theinvention.

From the foregoing, it should be appreciated that an improved method oftreating morbid obesity has been described. The method includes formingand placing implants in the walls of the stomach and/or pylorus toeffectively create barriers to gastric peristalsis and the forwardpropulsion of stomach contents and/or to alter the motility of thestomach contents through the modification of sensory motor nervousfeedback and control. The method is relatively non-invasive and servesto prolong satiety. Limiting gastric distensibility and prolonginggastric emptying times in this manner, while optionally enhancing thelower esophageal sphincter to inhibit gastroesophageal reflux, providesa novel, effective and safe method for treating a dangerous, yet common,condition.

The foregoing and other aspects of the invention are set forth in thefollowing claims.

What is claimed is:
 1. A method of treating a mammal having agastrointestinal tract extending through a stomach and a pyloricsphincter formed by a wall comprising: advancing a probe having anoptical viewing device to the implant site; introducing at least oneimplant into the wall; and monitoring introduction of the implant bytransabdominal or transesophageal ultrasound.
 2. The method of claim 1,wherein the probe is a gastroscope or endoscope.
 3. The method of claim1, wherein an implant forming solution comprising a biocompatiblepolymer and solvent is injected into wall.
 4. The method of claim 3,further comprising a contrast agent for facilitating visualization inthe mammal.
 5. The method of claim 3, wherein the wall has a musclelayer, the at least one implant being formed in the muscle layer of thewall.
 6. The method of claim 1, wherein an implant forming solutioncomprising a biocompatible prepolymer is injected into wall.
 7. Themethod of claim 6, further comprising a contrast agent for facilitatingvisualization in the mammal.
 8. The method of claim 6, wherein the wallhas a muscle layer, the at least one implant being formed in the musclelayer of the wall.